11 vessels
Transcript of 11 vessels
Diseases of BLOOD VESSELS
COMPONENTS• Intima, Media, Adventitia, M>A or A>M
• ENDOTHELIUM
• INTERNAL ELASTIC LAMINA
• ECM: Elastin (~aging), collagen, mucopolysaccharides
• Smooth Muscle
• Connective Tissue
• Fat
1) Blockage
(preceded by narrowing)
2) Rupture
Preceded by weakening)
TOPICS• Vascular wall
responses
• Congenital Anomalies
• Atherosclerosis
• Arteriosclerosis
• Hypertension
• Aneurysms
• Vasculitides
• Raynaud “phenomenon”
• Veins
• Lymphatics
• Tumors
• Interventions
DEFINITIONS• ARTERIO-sclerosis
• ATHERO-sclerosis
• Aneurysm
• Dissection
• Thrombus
• Hypertension
• Vasculitis/Vasculitides, infectious/NON-infectious (often-autoimmune)
• Varicosity
• DVT/Thrombo-phlebitis/Phlebo-thrombosis
DEFINITIONS• Lymphangitis
• Lymphedema
• Angioma/Hemangioma (generic)
• Lymphangioma
• Angiosarcoma (generic)
• Lymphangiosarcoma
NON-Specific Vascular WallResponse to Injury
• Endothelial “activation”
• Smooth Muscle cell roles
• Development, Growth, Remodeling
• Intimal “thickening”
ENDOTHELIAL CELLS• Recall Jeckyl/Hyde concept: maintain
hemostasis/cause thrombosis• Maintenance of Permeability Barrier • Elaboration of Anticoagulant, Antithrombotic,
Fibrinolytic Regulators• Elaboration of Prothrombotic Molecules • Extracellular Matrix Production (collagen,
proteoglycans) • Modulation of Blood Flow and Vascular Reactivity • Regulation of Inflammation and Immunity • Regulation of Cell Growth • Oxidation of LDL
ENDOTHELIAL CELL“ACTIVATORS” (Δ?)
• Cytokines
• Bacterial Products
• Hemodynamic Forces
• Lipid Products
• Viruses
• Complement• Hypoxia
VASCULAR SMOOTH MUSCLE• Vasoconstriction
• Vasodilatation
• Make ECM:– Collagen– Elastin– Proteoglycans
• Regulated by:– PROMOTORS: PDGF, endothelin, thrombin, etc.– INHIBITORS: Heparan SO4, NO, TGF-β
Vessel Growth & Remodeling
• The sum total of all the factors and processes involved in tissue injury and the body’s ability to grow vessels, develop new pathways, and re-perfuse areas in response to tissue and/or blood vessel injury.
CONGENITAL ANOMALIES• Arteriovenous fistulas • Also called ArterioVenous Malformation (AVM)• Common factor is abnormal communication
between high pressure arteries and low pressure veins
• Usually congenital, but can be acquired by trauma or inflammation
• Most often described in the brain as an AVM• Asymptomatic or with hemorrhage or
pressure effects
ARTERIO-SCLEROSIS• GENERIC term for ANYTHING
which HARDENS arteries– Atherosclerosis (99%)– Mönckeberg medial calcific
sclerosis (1%)
– Arteriolosclerosis, involving small arteries and arterioles, generally regarded as NOT strictly being part of atherosclerosis, but more related to hypertension and/or diabetes
ATHEROSCLEROSIS(classical)
• Etiology/Risk Factors
• Pathogenesis
• Morphology
• Clinical Expression
ATHEROSCLEROSIS(ala Robbins)
• *Natural History• *Epidemiology• *Risk Factors• *Pathogenesis• *Other Factors• *Effects• *Prevention
*NATURAL HISTORY
1) FATTY STREAK
2) ATHEROMA
(plaque)
3) THROMBUS
MORPHOLOGIC CONCEPTS
• Intimal Thickening• Lipid Accumulation• Streak• Atheroma• Smooth Muscle Hyperplasia and Migration• Fibrosis• Calcification• Aneurysm• Thrombosis
FATTY
STREAKS
PLAQUE
MILD ADVANCED
ADVANCED FEATURES
• RUPTURE
• ULCERATION
• EROSION
• ATHEROEMBOLI
• HEMORRHAGE
• THROMBOSIS
• ANEURYSM
FUN THINGS TO FIND:
Lumen, Fibrous cap (fibrous plaque), Lipid core, External Elastic Membrane thinning/destruction, Calcification, Neovascularization
*EPIDEMIOLOGY & RISK FACTORS
Epid./RiskFactors• Related to “development” of nation• US highest• 50-70% DECREASE 19632000.
Why?• AGE• SEX, M>F until menopause, estrogen
“protection”• GENETICS
MAJORfactors
• Hyperlipidemia
• Hypertension
• Cigarette Smoking
• Diabetes Milletus
Risk Factors for AtherosclerosisMajor MinorNON-modifiable Modifiable
Increasing age Obesity
Male gender Physical inactivity
Family history Stress ("type A" personality)
Genetic abnormalities Postmenopausal estrogen deficiency
High carbohydrate intake
Modifiable
Hyperlipidemia Alcohol
Hypertension Lipoprotein Lp(a)
Cigarette smoking Hardened (trans)unsaturated fat intake
Diabetes Chlamydia pneumoniae
MAJORfactors
• Hyperlipidemia
• Hypertension
• Cigarette Smoking
• Diabetes Milletus
HYPERLIPIDEMIA• Chiefly CHOLESTEROL,
LDL>>>>HDL• HDL mobilizes cholesterol FROM
atheromas to liver• LOW CHOLESTEROL diet is GOOD• UNSATURATED fatty acids GOOD• Omega-3 fatty acids GOOD• Exercise GOOD
CHOLESTEROL CLEFTS
HYPERTENSION• HYPERTENSION causes
ATHEROSCLEROSIS. Why?
• ATHEROSCLEROSIS causes HYPERTENSION. Why?
CIGARETTES• What more needs to be said?
DIABETES• If there was one disease
which I could challenge you to, as a dare, to PROVE to me that was NOT EXACTLY
THE SAME as atherosclerosis, it would be DIABETES! Any takers?
NON major factors• Homocysteinuria/homocysteinemia, related
to low B6 and folate intake
• Coagulation defects
• Lipoprotein Lp(a), independent of cholesterol. Lp(a) is an altered form of LDL
• Inadequate exercise, Type “A” personality, obesity (independent of diabetes)
• Protective effect of moderate alcohol? LIE!
PATHOGENESIS• “atherosclerosis is a chronic
inflammatory response of the arterial wall initiated by injury to the endothelium”
PATHOGENESIS SAGA• Chronic endothelial injury• LDL, Cholesterol in arterial WALL• OXIDATION of lipoproteins• Monocytes migrate endothelium• Platelet adhesion and activation• Migration of SMOOTH MUSCLE from media to
intima to activate macrophages (foam cells)• Proliferation of SMOOTH MUSCLE and ECM• Accumulation of lipids in cells and ECM
Main FOUR STARS of PATHOGENESIS SAGA
• 1) Endothelial Injury
• 2) Inflammation
• 3) Lipids
• 4) Smooth Muscle Cells, SMCs
Other Pathogenesis Considerations
• Oligoclonality of cells in plaque
• Chlamydia, CMV as endothelial injurers
PREVENTION PRINCIPLES
• Know what is preventable• Know what is MAJOR (vs. minor)• Know PRIMARY vs. SECONDARY
principles• Understand atherosclerosis begins in
CHILDHOOD• Risk factors in CHILDREN predict the
ADULT profile• Understand SEX, ETHNIC differences
NON ATHEROSCLEROSISVASCULAR DISEASES
• HYPERTENSION
• ANEURYSMS
• VASCULITIDES• VEIN DISORDERS
• NEOPLASMS
HYPERTENSION• “ESSENTIAL” 95%
• “SECONDARY” 5%
SECONDARY• Renal • Acute glomerulonephritis • Chronic renal disease • Polycystic disease • Renal artery stenosis • Renal artery fibromuscular dysplasia• Renal vasculitis • Renin-producing tumors
• Endocrine • Adrenocortical hyperfunction • (Cushing syndrome, primary aldosteronism, congenital adrenal hyperplasia, licorice ingestion)• Exogenous hormones (glucocorticoids, estrogen [including pregnancy-induced and oral
contraceptives], sympathomimetics and tyramine-containing foods, monoamine oxidase inhibitors)
• Pheochromocytoma, Acromegaly, Hypothyroidism (myxedema), Hyperthyroidism• Pregnancy-induced
• Cardiovascular: Coarctation of aorta, Polyarteritis nodosa (or other vasculitis)• Increased intravascular volume
• MISC: Increased cardiac output, Rigidity of the aorta, Neurologic, Psychogenic, Increased intracranial pressure, Sleep apnea, Acute stress, including, surgery
DEFINITION• 140/90
• SUSTAINED diastolic >90
• SUSTAINED systolic >140
BP = CO x PR
ALL Hypertension
ReninAngiotensinAldosteroneAXIS
• If the perfusion of the juxtaglomerular apparatus in the kidneys decreases, then the juxtaglomerular cells release the enzyme renin.
• Renin cleaves an inactive peptide called angiotensinogen, converting it into angiotensin I.
• Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE), which is found mainly in lung capillaries.
• Angiotensin II is the major bioactive product of the renin-angiotensin system. Angiotensin II acts as an endocrine, autocrine/ paracrine, and intracrine hormone.
GENETIC
ACQUIRED
HISTOPATHOLOGY ofESSENTIAL HYPERTENSION
“HYALINE” = BENIGN HTN. “HYPERPLASTIC” = MALIGNANT HTN. SYS>200 1) ONION SKIN 2) “FIBRINOID” NECR.
GENETICvs.
ENVIRONMENTAL• GENETIC UN-CONTROLABLE
• ENVIRONMENTAL CONTROLABLE– STRESS– OBESITY– SMOKING– PHYSICAL ACTIVITY– NaCl INTAKE
ANEURYSMS• TRUE vs. FALSE• ATHEROSCLEROTIC• NON-ATHEROSCLEROTIC
– CONGENITAL– LUETIC (SYPHILITIC)– TRAUMATIC– “MYCOTIC” (MIS-leading term)– 2° to VASCULITIS
• SACCULAR (i.e., “Berry”) vs. FUSIFORM• DISSECTION vs.NON-DISSECTION
ANEURYSMS• 2 CAUSES:
–1) ATHEROSCLEROSIS
–2) CYSTIC MEDIAL DEGENERATION
NORMAL elastic fibers DISRUPTED, FRAGMENTED elastic fibers
Most abdominal aortic aneurysms (AAA) occur between the renal arteries and the bifurcation of the aorta
ANEURYSMS(sequelae)
–RUPTURE
–OBSTRUCTION
–EMBOLISM
–COMPRESSION• URETER
• SPINE
–MASS EFFECT
THORACIC ANEURYSMS
–Encroachment–Respiratory difficulties–Dysphagia–Cough–Pain–Aortic valve dilatation–Rupture
DISSECTION
ANEURYSMS(luetic)
–Chiefly thoracic
–Follows an AORTITIS• PLASMA CELLS predominate
VASCULITIDES• TEMPORAL “GIANT CELL” ARTERITIS• TAKAYASU ARTERITIS• POLY (PERI) ARTERITIS NODOSA• KAWASAKI DISEASE• WEGENER’s GRANULOMATOSIS• THROMBOANGI(i)TIS OBLITERANS
(BUERGER DISEASE)• OTHER• INFECTIOUS
VASCULITIDES• Chiefly arterial• Infectious (5%) vs. Non-infectious (95%)• NON-infectious are generally “AUTO”-
IMMUNE. Why?• Persistent findings:
– Immune complexes– ANTI-NEUTROPHIL AB’s (Wegener’s)– ANTI-ENDOTHELIAL CELL AB’s (Kawasaki)
• Often DRUG related (Hypersensitivity, e.g.)
“TEMPORAL” ARTERITISaka, Giant Cell Arteritis, GCA
• ADULTS• Mainly arteries of the head and temporal
arteries are the most visibly, palpably, and surgically accessible
• BLINDNESS most feared sequelae• GRANULOMATOUS WALL inflammation
diagnostic• OFTEN associated with marked ESR
elevation to be then known as POLYMYALGIA RHEUMATICA
• Anti-NEUTROPHIL AB’s often POSITIVE
TEMPORAL ARTERITIShttp://www.path.uiowa.edu/cgi-bin-pub/vs/fpx_gen.cgi?slide=623&viewer=java&view=0&lay=iowa
TAKAYASU ARTERITIS• Involves aortic arch and other heavilly
elastic arteries, i.e., chief thoracic aorta branches
• FEMALES <40
• “PULSELESS” disease
• NECROSIS, Giant Cells also
POLY-(Peri-) ARTERITIS NODOSA (PAN)
• ANY MEDIUM or SMALL artery
• OFTEN visceral arteries
• Infarcts, aneurysms, ischemia
• CLASSICAL AUTOIMMUNE disease
• SEGMENTAL, TRANSMURAL, NECROTIZING (fibrinoid) inflammation
http://www.path.uiowa.edu/cgi-bin-pub/vs/fpx_gen.cgi?slide=584&viewer=java&view=0&lay=iowa
KAWASAKI DISEASE• CHILDREN <4
• CORONARY ARTERIES
• LEADING cause of ACQUIRED heart disease in children
• USA and JAPAN
• Fatal in only 1%
MICROSCOPIC POLYANGIITISHYPERSENSITIVITY VASCULITIS
LEUKOCYTOCLASTIC VASCULITIS• SMALL VESSELS OF ALL TYPES,
e.g., capillaries and veins too• FRAGMENTED NEUTROPHILS• aka, LEUKOCYTOCLASIA• aka, NUCLEAR “DUST”• Most are ALLERGIC reactions to
allergens like penicillin or strep• DERMATOLOGIST’s DISEASE
http://www.path.uiowa.edu/cgi-bin-pub/vs/fpx_gen.cgi?slide=634&viewer=java&view=0&lay=iowa
WEGENER GRANULOMATOSIS
• M>F, often in 40’s• ACUTE NECROTIZING GRANULOMAS OF
UPPER an LOWER respiratory tract• NECROTIZING GRANULOMATOUS
VASCULITIS of SMALL vessels of ALL types• Often renal involvement, “crescentic”
glomerulonephritis• ANTI-NEUTROPHIL-CYTOPLASMIC-AB’s
usually present
necrosis granulomasnecrosisgranulomasnecrosisgranulomasnecrosisgranulomas
necrosis granulomasnecrosisgranulomasnecrosisgranulomasnecrosisgranulomas
necrosis granulomasnecrosisgranulomasnecrosisgranulomasnecrosisgranulomas
THROMBOANGIITIS OBLITERANSBUERGER(‘s) Disease
• 100% caused by cigarette smoking
• MEN>>>F, 30’s, 40’s
• Often arteries are 100% obliterated, hence the name “obliterans”
• EXTREMITIES most often involved
http://www.path.uiowa.edu/cgi-bin-pub/vs/fpx_gen.cgi?slide=704&viewer=java&view=0&lay=iowa
OTHER VASCULITIDES
• SLE
• RHEUMATOID ARTHRITIS
INFECTIOUS ARTERITIDES
• ASPERGILLIS
• MUCORMYCOSIS
• “MYCOTIC” ANEURYSMS
NON ATHEROSCLEROSISVASCULAR DISEASES
• HYPERTENSION
• ANEURYSMS
• VASCULITIDES
• VEIN DISORDERS
• NEOPLASMS
FINAL TOPICS• Raynaud Phenomenon• Veins and Lymphatics
– Varicosities– Thrombophlebitis/Phlebothrombosis– SVC/IVC syndromes– Lymphangitis– Lymphedema
• Tumors: Benign, Intermediate (Borderline), Malignant
• Vascular Interventions: Angioplasty, Stents, Grafts
Raynaud “Phenomenon”• PRIMARY: (formerly Raynaud “DISEASE”)
– Digital PALLORCYANOSISHYPEREMIA– (WHITE)(WHITE) (BLUE)(BLUE) (RED)(RED)– Vasoconstriction usually triggered by COLD, emotion– Can be tip of nose, not only digits– Self Limited, Gangrene UN-common
• SECONDARY: (formerly Raynaud “Phenomen.”)– Atherosclerosos– SLE– Buerger Disease
WHITE
BLUE
RED
“Varicose” Veins• 20% of population, F>M
• Related to increased venous pressure, age, valve dysfunction
• Superficial veins of lower extremities most common
• PATH: 1) DILATED, 2) TORTUOUS, 3) ELONGATED, 4) SCARRED (phlebosclerosis), 5) CALCIFICATIONS, 6) NON-UNIFORM SMOOTH MUSCLE
• Conceptually like varices or hemorrhoids
THROMBOPHLEBITIS• 90% DEEP veins of the legs• IDENTICAL to PHLEBOTHROMBOSIS• Factors: CHF, Neoplasia (esp. GI, panc.
Lung adenocarcinomas “migratory” thrombophlebitis), pregnancy, obesity, post-op, immobilization, or any of the parts of Virchow’s triangle
• Sequelae: PE most feared• Symptoms: edema, cyanosis, heat, pain,
tenderness, but usually……..NONE!!!
SVC SYNDROME• Usually from bronchogenic CA
or mediastinal lymphoma
• DUSKY CYANOSIS of:–Head
–Neck
–Arms
IVC SYNDROME• Secondary to:
– NEOPLASMS (external compression)– ASCENDING THROMBOSIS from
FEMORALS, ILIACS– AAA, Gravid uterus
• Bilateral leg edema
• Massive proteinuria if renal veins involved (like nephrotic syndrome)
LYMPHANGITIS• From regional infections• Group-A beta-hemolytic strep most
common• Lymphatics dilated, filled with WBCs• Cellulitis usually present too• Lymphadenitis also usually follows• If lymph nodes cannot filter (process)
antigens enough septicemia
LYMPHEDEMA• Lymphatic channels blocked or
scarred or absent:– Post surgical
– Post radiation
– Filaria
– Congenital
– Tumoral (peau d’orange)
CHYLE• CHYLOUS ASCITES
• CHYLOTHORAX
• CHYLOPERICARDIUM
Vascular TUMORS• BENIGN (NEVER metastasize, in fact
some are not even TRUE neoplasms, but hamartomas)
• INTERMEDIATE (rarely metastasize)
• MALIGNANT (FREQUENT and EARLY metastases, like any other sarcoma lung)
BENIGN---------------------------------------MALIGNANT
Rare mitosis--------------------------Common mitosis
Mild, rare atypia------------Frequent, severe atypia
NO mets----------------------------Early, frequent mets
via BLOODSTREAM
HEMANGIOMA• Often a generic term for ANY benign blood
vessel tumor
• CAPILLARY (small vascular spaces)– Also called “juvenile”, often called “birth marks”– Usually regress with age
• CAVERNOUS (LARGE vascular spaces)– Also called “adult”– Usually do NOT regress
PYOGENIC GRANULOMA
• ORAL CAVITY MOST COMMON
• Histology like capillary hemangioma
• Regress
• Indistinguishable from normal granulation tissue
LYMPHANGIOMA• Small 1-2 mm
• Head and neck region
• Generally……RARE
• When large size and/or spaces present often called “CYSTIC HYGROMA”
GLOMUS TUMORGLOMANGIOMA
• 1 cm
• Most commonly under nail
• Painful
MISC. “BENIGN” TUMORS• -ectasias, telangiectasias• Nevus Flammeus, aka, port wine stain• Spiders (spider telangiectasias), ass. W.
pregnancy, cirrhosis• Osler-Weber-Rendu Disease (Hereditary
Hemorrhagic Telangiectasia)• Bacillary Angiomatosis, in HIV patients, caused
by bacilli of Bartinella species
INTERMEDIATE (BORDERLINE)VASCULAR NEOPLASMS
• Kaposi Sarcoma, KS– 1) Classic European, described 1872, NON-HIV– 2) African, pre-HIV, now HIV- and HIV+– 3) Transplant associated, HIV-– 4) AIDS KS, caused by HHV-8, aka KSHV
– PATCH PLAQUENODULE
• HEMANGIOENDOTHELIOMA (HETEROGENEOUS GROUP OF NEOPLASMS)
Diagnosis of vascular neoplasms may require the use of endothelial cell markers such as Factor VIII or CD-31, especially if clear cut
vascular spaces are difficult to see, especially if the tumor is UNDIFFERENTIATED enough to the
degree that endothelial lined spaces are NOT clearly seen.
MALIGNANT VASCULAR TUMORS
• ANGIOSARCOMA– May not look “vascular” at all– Severe atypia– Frequent and often bizarre mitoses– Behave as any sarcoma might, i.e., early
pulmonary metastases
• HEMANGIOPERICYTOMA– HETEROGENOUS group of disorders– Most commonly arising in pelvic retroperitoneum
VASCULAR INTERVENTIONS
• ANGIOPLASTY
• STENTS
• GRAFTS– Autologous (saphenous v., internal
mammary a.)– Synthetic (Teflon)
ANGIOPLASTIES• Plaque fracture (crackling sound)
• Dissection
• Arterial dilatation initially
• Restenosis ~ 6 months
STENTS• Metallic mesh• Permanently placed• Stays patent longer
than angioplasty• OFTEN DRUG COATED• Goals:
– Prevent thrombosis– Prevent spasm– Delay RE-stenosis
GRAFTS• 400,000 CABG grafts per year in USA• Saphenous v. vs. Internal mammary a. (internal
thoracic a.)• 50% patent after 10 years, for saphenous v.• 90% patent after 10 years, for mammary a.
• Endothelial and smooth muscle migration and proliferation key factors for success